1

Are collagen meniscus implants a reality?

2
3Gustavo Vinagre
4

5Department of Orthopaedic Surgery and Traumatology, Clnica Universidad de Navarra,

6Avenida Po XII 36, 31008 Pamplona, Navarra Spain
7
8Correspondence should be addressed to G. Vinagre, ldemil@unav.es

9
10
11Abstract
12Objective and method

The objective of this article is to determine the status of the collagen

13meniscus implants investigation, their indications and contra-indications and its role in the clinical
14outcome of the meniscal cartilage injuries.
15Results and conclusions

Meniscal cartilage regeneration is possible due to different scaffolds that

16facilitate migration and colonization with new meniscus-like matrix formation hosting cells
17mimicking native meniscal tissue. Selecting the suitable candidate is one of the key factors in
18achieving a successful outcome.
19
20Keywords

21Collagen Meniscus Implant (CMI) Meniscus Repair Meniscal Scaffold Cartilage Tissue
22Engineering
23
24Introduction
25Menisci represent a fundamental role in the knee joint [1, 8], playing a key role in the
26maintenance of knee homeostasis and its biomechanics [20]. The main functions of the menisci
27include force transmission, shock absorption, provision of joint stability, lubrication and
28adjustment to tibial surfaces, propioception, body weight distribution, pressure resistance, shock
29absorption, modulation of femoral condyle shape and joint stabilization during flexion and
30extension and lubrication of the knee joint [1, 7, 12].
31The number of meniscal lesions has increased markedly in recent years because of higher levels

32of participation in sport activities [5] and cartilage-like menisci can be found in osteoarthritis
33related to mechanical damage and aging [6].
34Treatment of meniscal lesions is the most common surgical intervention performed by orthopaedic

35surgeons today, with over 1 million surgical interventions involving meniscus performed annually
36in the United States and approximately 400 000 in Europe [27] and the arthroscopic meniscal
37resection is one of the most common surgical procedures performed in the world [15].
38The knee menisci are semilunar-shaped fibrocartilagenous structures interposed between the

39femoral condyle and tibial plateau [7] and contains fibrochondrocytes, with an abundant
40extracellular matrix [23].
41The subsequent loss of some degree of meniscal tissue alters this protective function by

42modifying the pattern of load distribution leading to osteoarthritis and irreversible joint damage
43[4, 26]. This condition has frequently been shown to lead to painful knee, chondral lesion, joint
44space narrowing, osteophyte formation with severe joint function impairment [15, 9].

45The extent of meniscectomy leading to clinically significant outcomes is unknown. However, it is

46now accepted that the larger the meniscectomy, the larger the decrease in the contact area and
47the larger the increase in the mean and peak contact stresses on the articular cartilage in the
48meniscectomized compartment as a result of the decreased contact area [27, 15]. Different animal
49meniscectomy models using meniscal scaffolds such as rabbit and dog have been studied [12, 13,
5023].
51The best treatment for meniscal injury is the meniscal repair preserving the meniscus by suturing

52the lesion [9] calling for the need to save the meniscus [14].
53Unfortunately, not all damaged menisci can be treated with minimum resection or repair,

54particularly for lesions in the avascular portion of the meniscus due to its limited healing
55potential [22]. This fact makes some large resections inevitable. For such irreparable lesions,
56partial meniscectomy is the current standard of care [27] due to the short operative time, low
57morbidity, low costs, fast recovery and usually good early results [33]. In these cases and in an
58effort to keep the knee functional and pain free, an interest in meniscal preservation techniques
59has increased over the last few decades and functional repair of the meniscus remains a
60significant challenge in orthopaedic surgery [22, 30].
61Meniscal tissue-engineering implants with proper pores geometry and architecture [16] were

62developed as a promising option for regeneration of partial native tissue loss [15, 31] and, in
63these cases, replacement of the removed meniscal tissue with a prosthetic meniscus that could
64provide a solution and prevent degeneration [9, 24, 35].
65
66Discussion
67Meniscal regeneration appears to require the physical presence of a scaffold to encourage

68successful migration and colonization with precursor cells and vessels, eventually leading to the
69formation of organized meniscal tissue.
70Until recently, there has only been 1 meniscus scaffold that has been shown to replace lost or
71damaged meniscus tissue in human clinical studies [27]: Collagen Meniscal Implant (CMI).
72Otherwise other materials such as bacterial cellulose gel or human autologous meniscus cells
73extended in high-density cultures have been used intended to promote cell migration and serve as
74a meniscal matrix implant [3, 8].
75The CMI was conceived to conduct meniscal regeneration in the early 80s. It has physical size
76and shape approximating the original human meniscus. The CMI surgical technique is less
77complex than the technique for meniscus transplantation and avoids problems of implant sizing,
78immunological reaction and disease transmission [4]. The implants are made of type I collagen
79fibres derived from bovine Achilles tendon. After the tendon tissue is trimmed and minced, the
80type I collagen fibres are purified by using various chemical treatments to remove non81collagenous proteins and lipids. Next, the purified collagen fibres are swelled in hyaluronic acid
82and chondoitin sulphate and then homogenized. The swollen collagen fibres plus the
83glycosaminoglycans are co-precipitated by the addition of ammonium hydroxide. The precipitated
84fibres are dehydrated, manually oriented in a mould, lyophilized, and chemically cross-linked.
85Finally, terminal sterilization is performed by irradiation.
86The CMI is not a prosthetic device. It is intended to provide a resorbable scaffold that will be
87replaced by the patients own tissue over time. Unlike meniscus allografts that are used to
88replace the entire meniscus, the CMI is designed to solely replace the irreparable damaged or
89missing portion of the meniscus in a chronic meniscal injury, not found to have any benefit for
90patients with an acute injury [19]. The ideal patient must have an intact meniscal rim and
91anterior and posterior horns for a good attachment and stability of the scaffold fixing it with
92proper suture materials [10]. Otherwise, would not accomplish the hoop stress law and the final
93construct will be extruded from the tibial plateau, resulting in a non-effective procedure.

94However, a case report has been described of semitendinosus tendon autograft for reconstruction

95of the meniscal wall supporting a collagen implant [2]. In addition, the surgically prepared site
96for the CMI must extend at least into the red-white zone of the meniscus to provide sufficient
97vascular supply, although mesenchymal stem cells/collagen-scaffold sandwiched implants in vitro
98has been made for the repair of white zone meniscal cartilage tears [17]. Patients are excluded if
99they had had a previous treatment with collagen or if they had an allergy to collagen,
100inflammatory arthritis or degenerative joint disease and evidence of osteonecrosis in the targeted
101area. It is also contraindicated in patients allergic to bovine or other animal derived products,
102with an overly sensititized immune system, systemic or local infection [25].
103The type I, bovine collagen meniscus scaffold purified from bovine Achilles tendon [1] is

104formerly called CMI (Menaflex, ReGen Biologics, Franklin Lakes, New Jersey) can only be
105implanted after partial meniscectomy because it requires the meniscal rim and horn to be
106properly fixed [27, 15].
107According to the available literature, meniscal substitution with the CMI provides significant pain

108relief and functional improvement after a minimum of 10 years` follow-up. The implant generally
109diminished in size [32], but the procedure proved to be safe and had a low rate of implant
110failure on a long-term basis [25] with absence of a specific clinically relevant inflammatory or
111immune response [18].
112A novel biodegradable, synthetic, acellular scaffold composed of aliphatic polyurethane (Actifit,

113Orteq Ltd, London, United Kingdom) is used for the treatment of medial or lateral irreparable
114partial meniscal tears. The Actifit polymer is a slowly degrading polymer with polycaprolactone
115and urethane segments. The degradation starts by hydrolysis of the ester bonds in the
116polycaprolactone segments. This process is expected to take about 5 years. The urethane segments
117are more stable than the polycaprolactone segments and will eventually be safely phagocytized by
118macrophages or giant cells or become integrated into the surrounding tissue [28].
119Preclinical canine studies with the scaffold have reported, at 3 months postimplantation, intensive
120integration with the periphery and complete infiltration of all pores of the implant with
121vascularized fibrous tissue that had produced an abundant extracellular matrix, showing abundant
122collagen type 1 antibody labeling throughout the implant. At 6 months after implantation, the
123scaffold was integrated with the peripheral capsule and was completely filled with tissue [27].
124 No difference in clinical and radiological outcomes between medial and lateral CMI seems to be
125observed at 12 months postoperatively [11], nevertheless medial CMI seems to provide better
126clinical and radiological outcomes at long-term follow-up compared to partial medial
127meniscectomy [34].
128The collagen meniscal implant appears to support regeneration with tissue ingrowth if given an

129appropriate environment and does not appear to be rejected, and it is resorbed over time [21,
13029].
131
132Conclusion
133Regeneration of meniscal cartilage is possible through the development of the meniscal scaffolds.
134The most benefit seems to appear in symptomatic patients with an irreparable chronic meniscal

135injury or chronic pain after partial meniscectomy, currently one of the most frequently performed
136orthopaedic surgeries.
137Various materials have been tested, but none had the properties required to restore normal

138function of a native meniscus. Therefore, the degradation time for these scaffolds may be too
139short and longer follow-up with large-scale studies are required in the near future and further
140improvements in the implant, model, and surgical technique are essential.

141
142 Contributions
143Dr. Vinagre was responsible for conceptualization and writing this paper.
144
145Conflict of interest
146The author report no conflict of interest or financial support.
147
148Acknowledgments
149Special thanks to Teresa Beitia and Fabiola de Goi.
150
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